acute on chronic liver failure

25. Other viral infections that cause ACLF are hepatitis A and E infections superimposed on chronic liver disease or hepatitis D superimposed on hepatitis B viral (HBV) infection. Laleman W, Simon-Talero M, Maleux G, et al. Prog Liver Dis. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure Authors European Association for the Study of the Liver. For all people diagnosed with cirrhosis on transient elastography, refer to a specialist in hepatology. 64. Once again, no details are provided as to the incidence and predictive factors for the development of ACLF post-TIPS insertion. It's a medical emergency that requires hospitalization. There are no clinical trials specifically evaluating the use of nutritional support in patients with ACLF. Am J Gastroenterol 2017;112:1495505. Predicting clinical outcomes of cirrhosis patients with hepatic encephalopathy from the fecal microbiome. Am J Gastroenterol 2019;114:8997. However, when mucosal bleeding does occur or invasive procedures are required in the presence of an abnormal TEG study, cryoprecipitate or prothrombin complex concentrate are the preferred low-volume alternatives to raise the fibrinogen level (74,76,78). Gastroenterology 2012;142:50512.e1. Singal AK, Bataller R, Ahn J, et al. Bajaj JS, Wong F, Kamath PS. The likelihood of fungal infections increases with greater number of organ failures, ACLF diagnosis, ICU transfer, diabetes, AKI, longer stay, and previous bacterial infection (87,105,106). The development of ACLF in patients with HBV infection seems to be driven by intense inflammation that is both sterile and infection-related (147). Bernuau J, Rueff B, Benhamou JP. There were lower rates of death in the stem celltreated arm at 72 weeks (21% vs 47%; P = 0.02) (192). Zhang Y, Zhao R, Shi D, et al. The presence of CKD predisposes the patient to other organ failures, which in turn makes reversal of superimposed AKI much more difficult (38). Kidney failure is the most common organ failure in patients with ACLF, no matter how it is defined. 150. Meersseman P, Langouche L, du Plessis J, et al. Careful large-volume paracentesis is recommended in patients with tense ascites (161). Moreno C, Deltenre P, Senterre C, et al. In highly selected patients with severe AAH not responding to optimal medical therapy and supportive measures, LT may be considered (135,136). Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. In fact, recent data have clearly shown that INR, although strongly linked with liver function in the absence of vitamin K deficiency, does not measure coagulation in patients with cirrhosis (72). 75. Enteral feeding should be used if the patient is unable to meet nutritional needs by mouth alone. Fungal dysbiosis in cirrhosis. Plauth M, Bernal W, Dasarathy S, et al. Data is temporarily unavailable. 57. Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): Comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models. See the full list here. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Bajaj JS, O'Leary JG, Tandon P, et al. ACLF developed in 17.5% of patients who underwent various other interventions, with RRT being the most common precipitant, followed by therapeutic paracentesis, non-ERCP endoscopies, and TIPS insertion. Comparison of dopamine and norepinephrine in the treatment of shock. Angeli P, Garcia-Tsao G, Nadim MK, et al. Liver Transpl 2015;21:8818. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. [1]Trey C, Davidson CS. Transplant Direct 2019;5:e490. Crit Care Clin 2016;32:43951. 138. Fungal pathogens are a particularly important source of infection in patients with ACLF, most of which are nosocomial (104). Hepatology 2012;56:232835. Gastroenterology 2019;156:1693706.e12. Therefore, it is essential to rule out infection in all patients with ACLF, but the level of suspicion for infection in patients with ACLF and hypocoagulability should be even higher. J Hepatol 2015;62:3329. The aetiology and the interval from onset of jaundice to the development of encephalopathy have a significant impact on prognosis. Subramanian KKK, Tandon M, Pandey CK, et al. The liver has many functions. Kaplan DE, Serper MA, Mehta R, et al. 73. Gastroenterology 2012;142:7829.e3. The management of fulminant hepatic failure. In a multicenter French and Belgian study, the combination of prednisone and pentoxifylline has not been found to be superior to prednisone alone (128). Acute-on-chronic liver failure: Getting ready for prime-time. The APASL definition of ACLF was used in this study. Incidence, predictors and outcomes of acute-on-chronic liver failure in outpatients with cirrhosis. avoid? GRADE guidelines: 1. Engelmann C, Thomsen KL, Zakeri N, et al. The CANONIC study from the EASL-CLIF consortium has identified therapeutic paracentesis and the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) as the nonsurgical interventions that may precipitate ACLF in admitted cirrhotic patients (36). The choice of antibiotics depends on local susceptibility patterns. Therefore, the results cannot be directly translated to patients in the west, and further studies are needed (185). Clin Gastroenterol Hepatol 2019;17:75665.e3. Artzner T, Michard B, Weiss E, et al. To date, there is no strong evidence that these artificial liver support systems are useful in the management of patients with ACLF. Liver Int 2016;36:113342. What role should acute-on-chronic liver failure play in liver transplant prioritization? In patients with cirrhosis and ACLF, we suggest against INR as a means to measure coagulation risk (very low quality, conditional recommendation). Vuyyuru SK, Singh AD, Gamanagatti SR, et al. When exercising clinical judgment, particularly when treatments pose significant risks, healthcare providers should incorporate this guideline in addition to patient-specific medical comorbidities, health status, and preferences to arrive at a patient-centered care approach. Kim SY, Yim HJ, Park SM, et al. 16. Expert Rev Gastroenterol Hepatol 2018;12:34150. Five-percent albumin is often used for rapid volume resuscitation, whereas for more sustained volume expansion, we recommend 25% albumin. Int J Environ Res Public Health 2020;17:1727. LT is the definitive treatment for HRS-AKI in cirrhosis. When vancomycin-resistant Enterococcus infection is suspected, linezolid or daptomycin should be used (163). Prediction of fungal infection development and their impact on survival using the NACSELD cohort. However, when TEG or ROTEM values are abnormal, clear cutoffs for type and number of transfusions needed have not been developed. Hepatology 2013;57:16513. 58. It should be noted that patients with CKD with a higher baseline sCr have a more severe course of AKI (38). More rapid completion of a 3-hour sepsis-care bundle and rapid administration of antibiotics is associated with lower risk-adjusted in-hospital mortality in patients with sepsis (91). 1970;3:282-98. http://www.ncbi.nlm.nih.gov/pubmed/4908702?tool=bestpractice.com. Garg V, Garg H, Khan A, et al. In patients with cirrhosis and suspected infection, we suggest early treatment with antibiotics to improve survival (very low quality, conditional evidence). Liver failure is one such condition, which involves multiple organs outside the liver. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This indicates that measures other than CTP and liver disease severity such as hemodynamics could be associated with ACLF prognosis. J Hepatol 2014;60:27581. 174. 158. Clinicians need to be aware of the association between hepatitis D viral and HBV infections. The quality of evidence is expressed as high (we are confident in the effect estimate to support a particular recommendation), moderate, low, or very low (we have very little confidence in the effect estimate to support a particular recommendation) based on the risk of bias of the studies, evidence of publication bias, heterogeneity among studies, directness of the evidence, and precision of the estimate of effect (2). Side effects include ischemic events in patients with underlying coronary artery disease or peripheral vascular disease, and the benefits of terlipressin use should be weighed against the risks of ischemia in patients with these underlying conditions. Albumin alone has not been shown to be effective for the treatment of HRS-AKI but is recommended as the adjunct therapy for HRS-AKI, both for its volume expanding and anti-inflammatory properties (4143). Hassan EA, Abd El-Rehim AS, Hassany SM, et al. Devarbhavi H, Choudhury AK, Sharma MK, et al. 142. 125. Asian Pacific Association for the Study of the Liver (APASL) defines ACLF as an acute hepatic insult manifesting as jaundice (serum bilirubin 5 mg/dL [85 mol/L]) and coagulopathy (international normalized ratio [INR] 1.5 or prothrombin activity < 40%) complicated within 4 weeks by clinical ascites and/or hepatic encephalopathy (HE) in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis and is associated with a high 28-day mortality. Extrahepatic organ failure is not required to make the diagnosis (, European Association for the Study of the Liver-Chronic LIver Failure (EASL-CLIF) consortium defines ACLF as a specific syndrome in patients with cirrhosis that is characterized by acute decompensation (AD), organ failure, and high short-term mortality. Model for end-stage liver disease-sodium underestimates 90-day mortality risk in patients with acute-on-chronic liver failuare. Specific author contributions: M.D.L. The severity of AKI is defined by stages. 86. Goldberg DS, Bajaj JS. PPIs have been shown to increase the rate of infections in patients with cirrhosis (111113). Such a situation occurs in patients with severe AAH, and infections or acute hepatitis, usually drug or viral, superimposed on chronic liver disease (158). According to the number of organ failures, ACLF is graded into three stages: ACLF-1 = single renal failure or single nonrenal organ failure if associated with renal dysfunction and/or cerebral dysfunction; ACLF-2 = two organ failures; and ACLF-3 . Therefore, it is critical to determine when and how the infection was acquired to appropriately choose the initial antibiotics (98). Recent data suggest that despite prophylactic antibiotics, 10% of patients on primary prophylaxis and 22% of patients on secondary prophylaxis still developed SBP with negative outcomes (56). 52. This needs to be recognized as a potential sequela and managed appropriately once the patient has recovered. Hepatology 2014;60:2506. Duan X-Z. Acute on chronic liver failure (ACLF) is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. Hemodynamic studies in acute-on-chronic liver failure. Stem Cell Translational Med 2012;1:72531. Such a change in renal function is known as acute-on-CKD, defined as a rise in sCr of 50% from baseline or a rise of sCr by 0.3 mg/dL (26.4 mol/L) in <48 hours in a patient with cirrhosis whose glomerular filtration rate is <60 mL/min for >3 months calculated using the 6-parameter modification of diet in renal disease formula (37). Louvet A, Thursz MR, Kim DJ, et al. The common features in all current definitions of ACLF include rapid worsening of chronic liver disease and high risk of mortality. Heavy alcohol use is defined as more than 3 standard drinks per day for women (approximately 40 g of alcohol) and 4 standard drinks per day for men (approximately 5060 g of alcohol). Sanyal AJ, Boyer T, Garcia-Tsao G, et al. The use of albumin in addition to antibiotics is recommended in patients with SBP to prevent HRS-AKI and subsequent organ failures but not recommended in non-SBP infections (54,55). Guyatt G, Oxman AD, Akl EA, et al. Bruns T, Reuken PA, Stengel S, et al. Clin Gastroenterol Hepatol 2017;15:152130.e8. Trebicka J, Fernandez J, Papp M, et al. Antibiotics should be de-escalated once cultures and sensitivities are available. Clin Nutr 2019;38:485521. Terlipressin is not currently US Food and Drug Administrationapproved but is expected to be approved in the near future. Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival. Of the 441 ERCP procedures performed, 158 were performed in patients with established cirrhosis, with decompensation being present at the time of ERCP in 71 cases (45%). In a nonrandomized study, patients with ACLF had a lower mortality if they were admitted on an NSBB than if they were not (116). CLIF-C ACLF (Acute-on-Chronic Liver Failure) Predicts mortality in acute-on-chronic liver failure. Gastroenterology 2018;155:156477. Increased risk of cognitive impairment in cirrhotic patients with bacterial infections. Respiratory failure is defined as PaO2/FiO2 of 200 or SpO2/FiO2 of 214 or the need for mechanical ventilation. Patients with chronic liver failure are often admitted with hepatic encephalopathy which describes a spectrum of neurologic impairment. Administration of albumin solution increases serum levels of albumin in patients with chronic liver failure in a single-arm feasibility trial. The article (CLD1189/CLD-21-0084.R1) "Surgical considerations regarding transplantation for the patient with acute on chronic liver failure" was published outside of this series issue "The Role of Liver Transplantation in Acute on Chronic Liver Failure". The aetiology and the interval from onset of jaundice to the development of encephalopathy have a significant impact on prognosis. Am J Gastroenterol 2006;101:15248; quiz 1680. Given this high risk of mortality, we recommend early advance care planning in all patients admitted with ACLF, even when under consideration for LT. Studies evaluating outcomes after LT in patients with ACLF have demonstrated acceptable outcomes after LT, but should be interpreted with caution, given inherent selection bias toward transplanting only those who are most likely to achieve favorable outcomes (200202). 146. However, no significant between-group differences were observed for the key clinical variables, such as duration of ventilation and 28-day mortality (59). World J Gastroenterol 2013;19:110410. Brain failure can be difficult to assess in intubated patients, and an evaluation for causes other than HE should be deferred until the patient is extubated. 41. Acute hepatic decompensation and the presence of infection are significant risk factors for the development of ACLF after surgery. Randomized-controlled trial of rifaximin versus norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis. J Hepatol 2021;75(3):61022. The current guideline represents the synthesis of the current and emerging data on ACLF as a major entity in patients with chronic liver disease. Hepatology 2019;70:41828. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381946 Thromboelastography-guided blood component use in patients with cirrhosis with nonvariceal bleeding: A randomized controlled trial. Get new journal Tables of Contents sent right to your email inbox, Clinical and Translational Gastroenterology, https://www.efclif.com/scientific-activity/score-calculators/clif-c-aclf, https://www.mayoclinic.org/medical-professionals/transplant-medicine/calculators/post-operative-mortality-risk-in-patients-with-cirrhosis/itt-20434721, https://optn.transplant.hrsa.gov/media/1192/0815-12_slk_allocation.pdf, https://www.aafp.org/news/health-of-the-public/20120214cdad-ppis.html, Acute-on-Chronic Liver Failure Clinical Guidelines, Articles in PubMed by Jasmohan S. Bajaj, MD, MS, FACG, Articles in Google Scholar by Jasmohan S. Bajaj, MD, MS, FACG, Other articles in this journal by Jasmohan S. Bajaj, MD, MS, FACG, Privacy Policy (Updated December 15, 2022). Moreover, none of the definitions requires the potential for reversibility of liver failure, which is the hallmark of an acute-on-chronic condition as opposed to chronic end-stage disease. Banares R, Nevens F, Larsen FS, et al. Bajaj JS, Reddy KR, Tandon P, et al. 161. Because serum C-reactive protein, procalcitonin, and bacterial DNA levels are often elevated in patients with cirrhosis, they are not diagnostic of infection, although persistently high levels correlate with mortality (9295). 44. AKI, altered mental status, and organ failure are often indicators of infection in patients with cirrhosis. Liver Int 2019;39:194353. Concentrating or avoiding IV medications that require large sodium loads can improve volume status in patients with ACLF. J Hepatol 2015;63:127284. * Identify the priorities of care for a patient admitted with acute or chronic liver failure. Bajaj JS, Moreau R, Kamath PS, et al. Specifically, systolic dysfunction is defined as left ventricular ejection fraction of 50% or an absolute global longitudinal strain of <18% or >22%. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios. Hypocoagulation found on TEG/ROTEM in ACLF is an independent marker of poor prognosis and is usually found in patients with systemic inflammatory response syndrome (SIRS). The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery. In patients with ACLF and altered coagulation parameters, we suggest against transfusion in the absence of bleeding or a planned procedure (low quality, conditional recommendation). N Engl J Med 2021;384:231730. Caraceni P, Riggio O, Angeli P, et al. Typically, a history of heavy alcohol use is present for greater than 5 years, but heavy alcohol use for a duration of as little as 6 months may cause AAH (126). Cao Z, Liu Y, Cai M, et al. EASL clinical practice guidelines on nutrition in chronic liver disease. Rating the quality of evidence. Management of renal dysfunction in inpatients with cirrhosis: Patients with stage 2 AKI are usually inpatients because they not only have significant renal dysfunction, but frequently, the precipitating event that leads to AKI also needs treatment. 90. 82. Hepatology 2016;63:201931. Acute liver failure is less common than chronic liver failure, which develops more slowly. Lancet. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS). Serum lactate may be elevated in patients with cirrhosis because of impaired hepatic clearance or because of tissue hypoxia. BP, blood pressure; GI, gastrointestinal; HE, hepatic encephalopathy; IV, intravenous; NG, nasogastric; PO, per oral. Because bacterial infections are a common precipitant of AKI, early diagnosis and treatment of bacterial infections are key to prevent AKI development. Liver Transpl 2019;25:5719. Am J Gastroenterol 2020;115(7):9891002. Liver biopsy is required to make a diagnosis of definite AAH, although patients may be entered into clinical protocols with a diagnosis of probable AAH (history of heavy alcohol use, typical clinical and laboratory presentation described above, and absence of confounding factors that may explain the clinical picture). 39. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: A systematic review and meta-analysis. Patients with cirrhosis who require surgery should be carefully selected because perioperative management of such patients also impacts survival. A recent study also demonstrated that prognosis of patients with cirrhosis and ACLF is similar to those admitted with similar level of critical illness in the absence of cirrhosis (18). Crit Care Med 2014;42:166675. Prevention of major precipitating factors such as infections and alcohol is critical in improving the prognosis of individual organ failures (brain, circulatory, renal, respiratory, and coagulation), and judicious use of antibiotics and antifungal medications is required. Vilstrup H, Amodio P, Bajaj J, et al. J Hepatol 2021;74:1097108. Lancet. Among patients with identical MELD or ACLF scores, the decision regarding proceeding with LT may depend on the presence or absence of frailty; portal hypertension; previous abdominal surgery; ventilator for HE vs respiratory failure; rising vs decreasing pressor requirement; and good vs marginal donor liver offer. Front Pharmacol 2019;10:1492. 193. This is especially relevant if patients still do not recover despite the measures instituted above. Am J Gastroenterol 2019;114:599606. SG has received honoraria from Mallinckrodt Pharmaceuticals for consulting work and from Salix Pharmaceuticals for speakers bureau and consulting work. Vaccinate patients with chronic liver disease against hepatitis A and hepatitis B if they are not already immune. Gut 2011;60:7029. Patients with cirrhosis of liver operated for non-transplant surgery: A retrospective analysis. Similarly, a higher neutrophil-lymphocyte ratio at admission portends an increased risk of mortality (96). Patients need to be monitored after they return to consciousness for critical carerelated post-traumatic stress. 60. 30. However, it is not clear whether among the 982 patients who survived, any had ACLF and survived (140). The intensive care unit course and outcome in acute-on-chronic liver failure are comparable to other populations. 19. Parenteral feeding should be considered in patients who cannot meet their nutritional needs using the gastrointestinal tract or in those with an unprotected airway, such as in patients with grade 34 HE. A randomized placebo-controlled trial. Hepatology 2018;68:232537. These guidelines are established to support clinical practice and suggest preferable approaches to a typical patient with a particular medical problem based on the currently available published literature. Choudhury A, Jindal A, Maiwall R, et al. Nosocomial infections are frequent and negatively impact outcomes in hospitalized patients with cirrhosis. CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt. A randomized trial. 102. 38. China L, Skene SS, Shabir Z, et al. Hepatology 2020;71:33445. 181. For any patient with cirrhosis admitted with altered mental status, the following 4 steps need to be undertaken concurrently (Figure 3): (i) airway management to prevent aspiration pneumonia; (ii) confirmation whether the condition is HE (or search for alternative causes as necessary); (iii) management of precipitating factors; and (iv) empirical therapy for HE (27,29). Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. http://www.ncbi.nlm.nih.gov/pubmed/4908702?tool=bestpractice.com J Hepatol 2019;71:94250. However, neither the risk of ACLF nor its outcomes have specifically been evaluated in patients with cirrhotic cardiomyopathy. Liver Int 2018;38(Suppl 1):12633. J Hepatol 2013;59:24350. A pulmonary arterial catheter to monitor pulmonary arterial pressure is recommended only in patients with pulmonary arterial hypertension. 198. Empiric therapy with meropenem and vancomycin is recommended in patients with cirrhosis and septic shock. Reverter E, Cirera I, Albillos A, et al. Although these data are provocative, many questions remain about the types of patients who would benefit from this therapy, precluding recommending use of stem cells in routine clinical practice. 6. Mookerjee RP, Pavesi M, Thomsen KL, et al. The role of ACLF prediction, precipitating factors, individual organ failures, management strategies, and impact on liver transplantation or end-of-life care is evolving. Gastroenterology 2018;155:42230.e1. Hepatology 2015;62:23242. Infection is common in these patients. 47. Although little is known about statins in ACLF in humans, in a recent rat model study of lipopolysaccharide-induced ACLF, pretreatment with simvastatin reduced portal pressures, inflammation, and oxidation and led to improved survival (122). NACSELD acute-on-chronic liver failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis. Soriano V, Sherman KE, Barreiro P. Hepatitis delta and HIV infection. The management of fulminant hepatic failure. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. PPI use may be associated with a higher risk of diarrhea and H2 blockers with a higher risk of delirium (62,63). Bajaj JS, Verna EC. Hepatol Int 2017;11:46171. Serum levels of metabolites produced by intestinal microbes and lipid moieties independently associated with acute on chronic liver failure and death in patients with cirrhosis. Bonnel AR, Bunchorntavakul C, Reddy KR. 159. After patients recover, they can often suffer from post-traumatic stress from their critical care experience (34). Gimson AE, O'Grady J, Ede RJ, et al. In patients with cirrhosis without ACLF, a rebalancing in coagulation occurs; however, in specific circumstances, hypercoagulability can be found (81,82). These definitions, however, do not serve to define the disease but rather reflect prognosis of the condition. 156. Surgery of any type in patients with cirrhosis is associated with significant risks of organ failure and ACLF development when compared with patients without cirrhosis. Lai JC, Tandon P, Bernal W, et al. Sundaram V, Shah P, Wong RJ, et al. Gastroenterology 2017;152:70615. In one small open-label controlled trial, 24 patients with ACLF secondary to HBV reactivation who were randomized to receive human mesenchymal stem cells were compared with 19 control patients who received saline placebo. Because PPIs impair the oxidative burst of neutrophils, they further impair immune function in patients with cirrhosis. 98. This is particularly true in areas of low and turbulent flow, such as the portal venous system. In determining factors associated with mortality at 2 months and 6 months, a combination of MELD score at baseline and response to treatment as determined by the Lille score at 7 days was superior to other combinations of scores (MDF + Lille; ABIC + Lille; and Glasgow alcoholic hepatitis score + Lille) (133). Liver Transpl 2021. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Piano S, Tonon M, Vettore E, et al. J Hepatol 2019;72(4):688701. Gastroenterology 2008;134:13529.

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